Chemical dosimetry is determined by labeling with tritium the alkyl group of an alkylating agent and measuring the alkylations per nucleotide of DNA in Drosophila melanogaster spermatozoa. The genetic effect is measured by determining the relative frequency of sex-linked recessive lethal mutations induced in D. melanogaster spermatozoa with an exposure to the nonlabeled alkylating agent equal to the dosimetry exposure. The importance of distinguishing between exposure of the whole organism, as measured by concentration in the feeding media, and dose to the germ cells, as measured by alkylation per nucleotide (AN) of spermatozoa DNA, is illustrated in the following observation. Methyl methanesulfonate (MMS) was found a more effective alkylating agent per unit time of exposure than ethyl methanesulfonate (EMS); however, MMS was less effective per unit dose, AN, in inducing sex-linked recessive lethal mutations. DNA alkylations accumulate to high levels in spermatids and spermatozoa because of lack of repair mechanisms and are lost in stored spermatozoa at a rate not exceeding the rate of hydrolysis of alkylated DNA. By feeding EMS for 24 hours in a concentration of 25mM, a dose of 1.4 x 10 to the minus 2nd power AN was observed. With 1.4% of the nucleotides alkylated, 57% of the x-chromosomes were hemizygously viable; therefore, ethylation per se is not very efficient in inducing mutations. The relative frequency of mutations increased linearly with the dose from a dose of 2.1 x 10 to the minus 4 power to 1.4 x 10 to the minus 2nd AN. No threshold was apparent and the statistical limit of the exponent was 1.0 plus or minus 0.1. This linear relation suggests no change in mechanism of mutagenesis occurs from low to high dose in Drosophila. A nonlinear relation was found between exposure and dose; when exposure was increased by a factor of 250 (from 0.1 to 25mM EMS in the feeding medium), dose was increased by only a factor of 68. By extrapolating down from our lowest dose of 2.1 x 10 to the minus 4 power alkylations per nucleotide with an observed frequency of 0.55 plus or minus 0.08% sex-linked recessive lethals, we estimate the doubling dose for sex-linked recessive lethals to be 4 x 10 to the minus 5th power AN. Current work is on establishing a dose response curve for methanesulfonate (MMS).